Vertebrate limb development Flashcards
(30 cards)
What are the 3 parts of a vertebrate limb along the proximal distal axis referred to
Stylopod - Zeugopod - Autopod
What is the structure of a limb bud
Mesenchymal cells surrounded by epithelial ectoderm
Distal ectoderm is thicker, this is the AER
ZPA in the posterior mesenchyme
What does the AER express
fgf8
what does the ZPA express
Shh
What does the dorsal epithelium of the limb bud express
Wnt7a
What hox genes lead to fore limb creation
hox4+5
what hox genes lead to hind limb creation
hox9/11
What T-box genes are expressed in each limb as a result of their hox genes
hox4+5 = tbx5
hox9/11 = tbx4 + pitx1
What do the T-box genes lead to the expression of in Limbs
FGF10 through Wnt signalling
Where is FGF10 expressed in the limb bud and what does it do
In the mesenchyme as this is where the Hox genes were active
It causes mesenchymal cells to proliferate, leading to outgrowth of the limb bud
How does FGF10 interact with the AER
FGF10 induces Wnt3a in Aer cells which upregulates fgf8 expression.
fgf8 acts on mesenchymal cells by increasing expression of FGF10
What happens when FGF is expressed ectopically
it is sufficient for limb bud creation.
If placed between two Hox domains it expands the expression of these domains to form a chimeric limb
What is the progress zone and how is it maintained
The zone in the distal limb bud mesenchyme where proliferation as a result of fgf8 signalling occurs. FGF8 also maintains the zone by inhibiting proliferation of the cells that see it.
How do cells leave the progress zone
cells in the proximal progress zone are pushed out by cells further in the progress zone proliferating
What is the progress zone model for proximal-distal patterning of the limb
That time spent in the progress zone determines the fate of the cells that leave it.
Cells that are pushed out first spent the least amount of time in it and therefore form stylopod, whilst those that are kicked out later form Zeugopod and then autopod.
This is determined using Hox genes
Which hox genes pattern the d-p axis in limbs
Stylopod- hox 10
Zeugopod- hox 11
autopod- hox 12+13
What is the signal model for limb patterning
Levels of Retinoic acid were shown to pattern this axis. High levels resulted in stylopod formation in Mice
What was the solution to having two different models
They were combined into the signal-progress zone model
where RA specialises proximal stylopod fate at early stages and progress zone specialises the rest once the AER forms
How is the A-P axis patterned in a limb
The ZPA secretes Shh which acts as a morphogen, patterning the limb. it originates in the posterior of the limb.
What was Shh shown to be capable of inducing in chicks
Digits 1+2+3
(In increasing Shh conc order)
Why was this not sufficient to conclude how this pattered human digits
we have 5 digits. So not enough fates in the shh gradient to specify such.
How does Shh specify digit 4 or 5 fates?
Digits 4 + 5 originate from ZPA tissue
The time spent exposed to Shh was shown to pattern these digits in Mice (4+5) and Chick feet (4)
How is time exposed to shh measured
Shh causes GliA to not be turned into GliR (which happens in the absence of Shh)
The ratio of GliA to GliR is used to determine exposure
What are the products of high GliA:R ratio and how does it pattern digits 4 + 5
It activated Ptch1, Gremlin1 and tbx genses
Tbx2 patterns digit 4
Tbx3 patterns digit 3
